초록
<P>Terpenoids represent the largest class of natural products, some of which are resources for pharmaceuticals, fragrances, and fuels. Generally, mass production of valuable terpenoid compounds is hampered by their low production levels in organisms and difficulty of chemical synthesis. Therefore, the development of microbial biosynthetic platforms represents an alternative approach. Although microbial terpenoid-production platforms have been established in <I>Escherichia coli</I> and yeast, an optimal platform has not been developed for <I>Streptomyces</I> species, despite the large capacity to produce secondary metabolites, such as polyketide compounds. To explore this potential, we constructed a terpenoid-biosynthetic platform in <I>Streptomyces reveromyceticus</I> SN-593. This strain is unique in that it harbors the mevalonate gene cluster enabling the production of furaquinocin, which can be controlled by the pathway specific regulator Fur22. We simultaneously expressed the mevalonate gene cluster and subsequent terpenoid-biosynthetic genes under the control of Fur22. To achieve improved <I>fur22</I> gene expression, we screened promoters from <I>S.？reveromyceticus</I> SN-593. Our results showed that the promoter associated with <I>rvr2030</I> gene enabled production of 212 ± 20 mg/L botryococcene to levels comparable to those previously reported for other microbial hosts. Given that the <I>rvr2030</I> gene encodes for an enzyme involved in the primary metabolism, these results suggest that optimized expression of terpenoid-biosynthetic genes with primary and secondary metabolism might be as important for high yields of terpenoid compounds as is the absolute expression level of a target gene(s).</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/asbcd6/2017/asbcd6.2017.6.issue-12/acssynbio.7b00249/production/images/medium/sb-2017-00249q_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/sb7b00249'>ACS Electronic Supporting Info</A></P>